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MARISSA B. LUKBAN, MD, FPPS, FPNA, FCNSPUniversity of the Philippines - College of MedicineDepartment of Pediatrics and Neurosciences
PIDSP 19thAnnual ConventionFebruary 16 2012CNS INFECTIONS :Spotlight on BacterialMeningitis
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To present the epidemiological picture ofbacterial meningitis worldwide and locallyPhilippine General Hospital)
To review the clinical practice guideline onthe performance of lumbar puncture inchildren with a first febrile seizures
To highlight the various ancillary testsavailable in the diagnosis of bacterialmeningitis To discuss the current recommendations onantibiotic management of bacterialmeningitis
Objectives:
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Case FatalityRatesBacterialMeningitisA View of thePast 90 years1910-2000)
Swartz, NEJM2004
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Active
Bacterial
Core
Surveillance
Whitney
NEJM 2003
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Brouwer
2010
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3188 pts with Bacterial Meningitis;466/3155 (14.8%) died31% DECREASE in incidence comparing 1998-99 vs 2006-07Median age: INCREASE from 30.3 yrs vs 41.9 yrsMost common organism: Strep Pneumoniae, Group B Strep,Neisseria, Hemophiluns influenze, Listeria
Thigpen NEJM 2011
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Frequency Distribution of Bacterial Meningitis inPhilippine General Hospital 2002-20065 year survey)
0
10
20
30
40
50
2002 2003 2004 2005 2006
HIB Pneumo Others/culture negative
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0
10
20
30
40
50
2002 2003 2004 2005 2006 2010 2011
HIB Pneumo Others/culture negative
Philippne General HospitalDepartment of PediatricsInpatient Census 2010-2011)
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Philippine General Hospital Department ofPediatrics Inpatient Census 2011)116 in patient admissions with meningitis
63 (54%) pts with tuberculous meningitis
46 (39% ) pts with bacterial meningitis
7 (6%) pts with viral/aseptic meningitis
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Philippine General Hospital Department ofPediatrics Inpatient Census 2011)
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Diagnostic ExaminationsTo diagnose bacterial meningitis CSFexamination is mandatory. CSF culture
is the gold standard for diagnosisand it is obligatory to obtain the invitro susceptibility of the causativeorganism to rationalize treatment
Van de Beek, NEJM, 2006
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PPS/PNA/CNSP 2004Clinical Practice Guideline on thefirst Febrile Seizure
Clinical Question: Among children with a first
febrile seizure, is lumbar puncture recommendedto rule out meningitis
CSF analysis is not the test that confirms the
diagnosis of febrile seizure per se
CSF analysis is the gold standard for the
alternative diagnosis of meningitis
AGE plays a crucial role in decision to do lumbar
puncture
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Local Studies on the prevalence of bacterial meningitisin children presenting with a first febrile seizure
Mangubat & Robles (East Avenue Medical Center)
Retrospective study of 198 children aged 3
months to 6 years
1% prevalence
Dilangalen & Perez (Cotabato Regional and Medical
Center)
Retrospective study of 339 children
7%prevalence
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Local Studies on the prevalence of bacterial meningitisin children presenting with a first febrile seizure San Nicolas & Lukban (Philippine General
Hospital)
Prospective study on validity indices of clinicalparameters in predicting lumbar puncture yield
of children with febrile seizures -11/50 (22%)abnormal CSF suggestive of meningitis
Discrimate factors in the clinical signs and
symptoms that differentiate children with
meningitis (70% identified) Complex febrile seizure
Fever of more than 3 days
Vomiting or drowsiness at home
Physician visit in past 48 hours
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Significant Clinical Parametersassociated with Bacterial Meningitis duration of fever of more than 3 days
the presence of anorexia, vomiting and sleepdisturbances
a physician consult within 48 hours prior toseizures
the presence of ear discharge
abnormal neurologic findings like nuchal rigidityand focal signs
depressed level of consciousness and
occurrence of seizures at the Emergency Room.
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Philippine Clinical Practice Guideline on the firstFebrile SeizureRECOMMENDATION STATEMENTLumbar puncture is strongly recommended for
children below 18 months for a first simple febrileseizure.
For those children >/= 18 months of age, lumbarpuncture should be performed in the presence ofclinical signs of meningitis (meningeal signs,sensorial changes)
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Diagnostic Examinations:The CSFRelationshipbetween serum
and CSF glucose
is highly linear
For every
increase of 1
mg/dl of serumglucose, CSF
glucose levels
increase by 0.56
mg/dl (95% CI
0.56-0.57 R2 0.94)
Nigrovic,
NEJM, 2012
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The Cerebrospinal Fluid Exam
20 USA ER Departments 2001-2004
Antibiotic pretreatment = received within 72 hrs from LP
Rates of positive gram stain did not differ
Rates of positive CSF and blood cultures lessNot associated with total WBC and neutrophil count
Increased glucose and decreased protein content
Nigrovic 2008
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Ancillary Diagnostic ExaminationsGram stainingBlood Culture
Latex Agglutination antisera
directed against capsularpolysaccharide of meningeal pathogen
PCR presence of bacterial DNA inCSF
Skin biopsy
Serum inflammatory markers
Increased serum procalcitonin
Increased C reactive protein
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Sensitivities of various diagnostic tests todetermine microbial etiologies of patients
with community acquired bacterialmeningitis
Brouwer 2010
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Prognostic Factors related to Sequelaeand Poor Outcome
Presence of seizures
Low CSF glucoseHigh CSF protein
Absence of rash
Positive blood culture
Etiology Pneumococcal and Meningocoocal
Vasilopoulou, Greek Meningitis Registry
BMC Infectious Disease 2011
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RECOMMENDATIONS ONTREATMENTBased on subgroups according to age andcommon organisms
Guided by prevailing antibiotic susceptibilityand resistance in the region
Generics Law
Clinical setting
Malnutrition
Finances
Access to vaccination
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CLINICALSUBGROUP
EMPIRIC THERAPY PREDOMINANTORGANISMS
NEONATE,EARLY ONSET
Ampicillin 150 mkday [q8h]plus Gentamicin 5mkday [q12h]or Cefotaxime 100-150mkday[q8-12] or Ceftriaxone 80-100mkday [q12-24h]
S. Agalactiae,E. Coli, ListeriaMonocytogenes
NEONATE,LATE ONSET
Ampicilllin 200mkday [q6-8h]plus Gentamycin 7.5 mkday [q8h] or Cefotaxime 150-200mkday [q6-8h]
S. Agalactiae, L.monocytogenes, Gram negativebacilli
INFANTS ANDCHILDREN
Cefotaxime 225-300 mkday[q6-8h] or Ceftriaxone 80-100
mkday [q12-24h] plusvancomycin 60mkday [q6h]*(if with high cephalosporinresistance)
S. Pneumoniae,N. meningitidis
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CLINICALSUBGROUP
EMPIRIC THERAPY PREDOMINANTORGANISMS
ADULTS Expanded spectrum
cephalosporin plusVancomycin 3060 mkday[q8-12h] *
Strep Pneumoniae,
Neisseria Meningitidis
ELDERLY ANDIMMUNO-COMROMISED
Expanded spectrumcephalosporin plus ampicillin12g/day [q4h] plusVancomycin 30 60mkday [q8-12h]*
S. Pneumoniae, N.MeningitidisL. Monocytogenes
COMMUNITYACQUIREDRECURRENT
Expanded spectrumcephalosporin plusVancomycin 3060 mkday
[q 8-12h]*
S. Pneumoniae, N.Meningitidis, H.Influenzae
NOSOCOMIAL Vancomycin 30-45 mkday [q8-2] plus Ceftazidime 6g/day[q 8h] or Meropenem 6g/day[q 8h]
S. Aurerus, SEpidermidis, aerobicgram negative bacilli
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MICROORGANISM STANDARD
THERAPY
ALTERNATIVE THERAPY
HEMOPHILUSINFLUENZAE
B LACTAMASE (-) Ampicillin Ceftriaxone/Cefotaxime;
Cefipime;Chloramphenicol;Aztreonam;Fluroquinolone
B LACTAMASE (+) Ceftriaxone/Cefotaxime
Cefipime;Chloramphenicol;
Aztreonam;Fluroquinolone
BLNAR Ceftriaxone/Cefotaxime plusMeropenem
Ceftriaxone/Cefotaximeplus Fluroquinolone
Brouwer 2010
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MICROORGANISM STANDARDTHERAPY
ALTERNATIVETHERAPY
STREPTOCOCCUSPNEUMONIAE
PENICILLINMIC 2.0UG/ML
Vancomycin plusthird gencephalosporin
Ceftiaxone/Cefotaxime plusmoxilocaxin
STREPTOCOCCUS
PYOGENES
Penicillin Ceftriaxone/
Cefotaxime
STREPTOCOCCUSAGALACTIAE
Ampicillin orPenicillin G(may need to addaminoglycoside)
Ceftriaxone/Cefotaxime
Brouwer 2010
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MICROORGANSIM STANDARDTHERAPY
ALTERNATIVETHERAPY
NEISSERIAMENINGITIDIS
PENICILLIN
MIC < 0.1 UG/ML
Penicillin G or
Ampicillin
Ceftriaxone/
Cefotaxime;Chloramphenicol
PENCILLINE MIC 0.1-1UG/ML
Ceftriaxone/Cefotaxime
Chloraphenicol;Fluroquinolone;Meropenem
Brouwer 2010
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MICROORGANISM STANDARDTHERAPY
ALTERNATIVETHERAPY
STAPHYLOCOCCUSAUREUS
METHICILLIN
SENSITIVE
Oxacillin or
nafcillin
Vancomycin,
Meropenem,Linezolid,Daptomycin
METHICILLINRESISTANT
Vancomycin Trimethoprim-Sulfa; Linezolid;Daptomycin
STAPHYLOCOCCUSEPIDERMIDIS
Vancomycin Linezolid
Brouwer 2010
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Vital Role of PediatriciansThere remains a lot to be done toreplicate the success of high-incomecountries in decreasing the incidence ofbacterial meningitis thru wide spread
vaccination in resource-poor countrieslike the Philippines.
There is a need for local government
initiatives to make vaccinations moreaccessible to all beyond the EPIprogram.
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Vital Role of PediatriciansThe pediatrician is strategicallysituated as he/she can act as anadvocate for the prevention ofmeningitis and is the key to averting the
disastrous complications of this diseasethru early recognition and appropriatemanagement.
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Thank you